The role of the Na-K pump in regulating intracellular concentrations of Na and K is well established. Structural changes in the pump protein or in the cell membrane in the vicinity of the pump may alter the normal activity of the pump. A structural change in the pumps (or in the cell membrane near the pumps) has been demonstrated in certain sheep and goats. This alteration increases the affinity of the pump for intracellular K, resulting in cells which are low in intracellular K and reciprocally high in intracellular Na. Animals with this structural change are called LK in contrast to the normal, or HK animals. The LK characteristic, which is genetically determined, has antigenic properties. An antibody to this LK characteristic, called anti-L, can be obtained by injection of LK red cells into an HK animal. The antibody, upon interaction with the antigen, reduces the inhibition of the Na-K pump by internal K, resulting in an increase in intracellular K concentration and a reduction in concentration of intracellular Na. The mechanism by which the externally located antigen increases intracellular affinity for K is not known. In addition, the mechanism by which anti-L interacts with the LK antigen to reduce the intracellular affinity for K is also not known. This proposal is directed towards elucidating these mechanisms. Further information about the relationship between the structure of the pump protein and its kinetic activity is expected to be obtained using the techniques developed for these studies.